In an interim analysis of a Chinese phase II/III trial (ZSAB) reported in The New England Journal of Medicine, Shi et al found that a neoadjuvant GOLP regimen (gemcitabine plus oxaliplatin, lenvatinib, and a PD-1 inhibitor [toripalimab]) improved event-free survival vs no neoadjuvant treatment in patients with resectable high-risk intrahepatic cholangiocarcinoma.
Study Details
In the multicenter open-label trial, 178 patients were randomly assigned between January 2021 and February 2025 to receive neoadjuvant GOLP followed by curative resection (n = 88) or curative resection alone (n = 90). GOLP consisted of gemcitabine at 1 g/m2 on days 1 and 8 and oxaliplatin at 85 mg/m2 on day 1 every 3 weeks for three cycles, toripalimab at 240 mg every 3 weeks for three cycles, and lenvatinib at 8 mg once daily for 9 weeks. All patients received adjuvant capecitabine at 2,500/mg2 in two divided doses on days 1 through 14 of a 3-week cycle for eight cycles. The primary endpoint was event-free survival.
Key Findings
At the interim analysis at a median follow-up of 16.9 months, median event-free survival was 18.0 months (95% confidence interval [CI] = 13.8–27.6 months) in the GOLP group vs 8.7 months (95% CI = 7.2–12.4 months) in the control group (P < .001). Rates at 24 months were 37% (95% CI = 26%–53%) vs 25% (95% CI = 16%–39%), respectively.
Death occurred in 20% of patients in the neoadjuvant group vs 34% of the control group, and overall survival rates at 24 months were 79% vs 61%, with the P value of .005 not reaching the prespecified significance criterion of P = .00019.
During neoadjuvant treatment, treatment-related adverse events of grade 3 or higher occurred in 26% of the neoadjuvant regimen group, most commonly decreased neutrophils (17%) and decreased white blood cells (7%). Immune-mediated adverse events of any grade occurred in 36% of patients, most commonly rash (10%) and hypothyroidism (10%). The two groups had similar durations of surgery, intraoperative blood loss, and postoperative length of stay. Surgical complications occurred in 24% of the neoadjuvant group vs 34% of the control group. No treatment-related deaths were observed.
The investigators concluded, “Neoadjuvant GOLP led to significantly longer event-free survival than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk intrahepatic cholangiocarcinoma.”
Guo-Ming Shi, MD, Jian Zhou, MD, and Jia Fan, MD, of the Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China, are the corresponding authors for The New England Journal of Medicine article.
DISCLOSURE: The study was funded by the Clinical Research Plan of Shanghai Hospital Development Center and others. For full disclosures of the study authors, visit nejm.org.
